Fujun Yang, Shumeng Li, Qingyu Ji, Hongyuan Zhang, Mingyang Zhou, Yuequan Wang, Shenwu Zhang, Jin Sun, Zhonggui He, Cong Luo
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引用次数: 0
摘要
由于载氧材料生物相容性差、载氧性能不理想、细胞耗氧量异常高等原因导致缺氧缓解不充分,肿瘤缺氧干预模式的临床转化仍未达到预期。本文精心研究了一种基于模块化氟化原药设计和共组装纳米技术的无载体氧气纳米罐,它是通过将氟化原药 pyropheophorbide a(PPa)(FSSP)和耗氧量抑制剂(阿托伐醌,ATO)进行分子纳米组装而制成的。这种纳米罐能够在实现充分富氧的同时抑制肿瘤内的耗氧量,从而彻底缓解肿瘤缺氧。值得注意的是,FSSP 中的氟化模块不仅有利于 FSSP 和 ATO 的共同组装,还能使纳米组件更容易携带氧气。正如预期的那样,它显示出卓越的携氧能力、良好的药代动力学、可按需激光触发的 ATO 释放、闭环肿瘤缺氧缓解,以及对 PPa 介导的体外和体内 PDT 的显著增强。这项研究为肿瘤缺氧干预增强癌症治疗提供了一种新的纳米治疗范例。
Modular Prodrug-Engineered Oxygen Nano-Tank With Outstanding Nanoassembly Performance, High Oxygen Loading, and Closed-Loop Tumor Hypoxia Relief.
The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen-carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption-caused insufficient hypoxia relief. Herein, a carrier-free oxygen nano-tank based on modular fluorination prodrug design and co-assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano-tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co-assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on-demand laser-triggerable ATO release, closed-loop tumor hypoxia relief, and significant enhancement to PPa-mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention-enhanced cancer therapy.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.